Nicotine was shown to be neuroprotective in different experimental models and in some epidemiological studies. The well-known health risk caused by nicotine use involves vascular damage. but almost no neuronal damage. Nicotine is an addictive drug that causes behavioral modifications and biochemical changes in the brain. Different schedules of nicotine administration produce distinct behavioral and physiological effects. We propose that some of these behavioral and physiological states correspond to different degrees or modes of nicotine-mediated neuroprotection or otherwise modified susceptibility to excitotoxicity. Nicotine is usually taken in by humans in a complex mixture. We described that cembranoids from tobacco and Caribbean corals inhibit the effect of nicotine. Recently, we found cembranoids in cigarette smoke. Therefore it is plausible that cembranoids play a role in the health effects of nicotine. Since nicotine is known to induce the synthesis of neurotrophins, this could explain part of the nicotine-induced neuroprotection. It is proposed here to use rats treated with different nicotine administration regimens to test behavior, neurotrophin, concentration and expression in several brain areas and susceptibility to NMDA toxicity of acute brain slices. In the last part of this project it is proposed to use immunohistological methods to study the distribution of neurotrophins and their mRNAs in brain sections. In addition, it is proposed to measure the effect of different nicotine pre-treatments on the extent of damage after experimental focal ischemia.